P20D2_HUMAN
ID P20D2_HUMAN Reviewed; 436 AA.
AC Q8IYS1; B4DYJ2; Q5T7J9; Q6MZV2; Q86XD9;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Xaa-Arg dipeptidase;
DE EC=3.4.13.4 {ECO:0000269|PubMed:24891507};
DE AltName: Full=Beta-Ala-Lys dipeptidase {ECO:0000303|PubMed:24891507};
GN Name=PM20D2 {ECO:0000303|PubMed:24891507, ECO:0000312|HGNC:HGNC:21408};
GN Synonyms=ACY1L2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 371-436.
RC TISSUE=Salivary gland;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24891507; DOI=10.1074/jbc.m114.576579;
RA Veiga-da-Cunha M., Chevalier N., Stroobant V., Vertommen D.,
RA Van Schaftingen E.;
RT "Metabolite proofreading in carnosine and homocarnosine synthesis:
RT molecular identification of PM20D2 as beta-alanyl-lysine dipeptidase.";
RL J. Biol. Chem. 289:19726-19736(2014).
CC -!- FUNCTION: Catalyzes the peptide bond hydrolysis in dipeptides having
CC basic amino acids lysine, ornithine or arginine at C-terminus.
CC Postulated to function in a metabolite repair mechanism by eliminating
CC alternate dipeptide by-products formed during carnosine synthesis.
CC {ECO:0000269|PubMed:24891507}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanyl-L-lysine + H2O = beta-alanine + L-lysine;
CC Xref=Rhea:RHEA:59608, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:57966, ChEBI:CHEBI:143161; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59609;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-alanyl-L-ornithine + H2O = beta-alanine + L-ornithine;
CC Xref=Rhea:RHEA:59612, ChEBI:CHEBI:15377, ChEBI:CHEBI:46911,
CC ChEBI:CHEBI:57966, ChEBI:CHEBI:143162; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59613;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-lysine = 4-aminobutanoate + L-
CC lysine; Xref=Rhea:RHEA:59620, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:59888, ChEBI:CHEBI:143159; EC=3.4.13.4;
CC Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59621;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-ornithine = 4-aminobutanoate +
CC L-ornithine; Xref=Rhea:RHEA:59624, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:46911, ChEBI:CHEBI:59888, ChEBI:CHEBI:143160;
CC EC=3.4.13.4; Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59625;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(2)-(4-aminobutanoyl)-L-arginine = 4-aminobutanoate +
CC L-arginine; Xref=Rhea:RHEA:59628, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:32682, ChEBI:CHEBI:59888, ChEBI:CHEBI:143158;
CC EC=3.4.13.4; Evidence={ECO:0000269|PubMed:24891507};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59629;
CC Evidence={ECO:0000305|PubMed:24891507};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=5.4 mM for beta-alanyl-L-lysine {ECO:0000269|PubMed:24891507};
CC KM=6.5 mM for beta-alanyl-L-ornithine {ECO:0000269|PubMed:24891507};
CC Vmax=0.30 umol/min/mg enzyme toward beta-alanyl-L-lysine
CC {ECO:0000269|PubMed:24891507};
CC Vmax=0.43 umol/min/mg enzyme toward beta-alanyl-L-ornithine
CC {ECO:0000269|PubMed:24891507};
CC -!- INTERACTION:
CC Q8IYS1; Q9Y5P4-2: CERT1; NbExp=3; IntAct=EBI-11339910, EBI-11156432;
CC Q8IYS1; Q8NE01: CNNM3; NbExp=3; IntAct=EBI-11339910, EBI-741032;
CC Q8IYS1; Q5D0E6-2: DALRD3; NbExp=3; IntAct=EBI-11339910, EBI-9090939;
CC Q8IYS1; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-11339910, EBI-742054;
CC Q8IYS1; Q9NVH1: DNAJC11; NbExp=3; IntAct=EBI-11339910, EBI-1055336;
CC Q8IYS1; Q9UM22: EPDR1; NbExp=3; IntAct=EBI-11339910, EBI-946972;
CC Q8IYS1; Q9GZV7: HAPLN2; NbExp=3; IntAct=EBI-11339910, EBI-11956675;
CC Q8IYS1; P23276: KEL; NbExp=3; IntAct=EBI-11339910, EBI-746662;
CC Q8IYS1; O95678: KRT75; NbExp=3; IntAct=EBI-11339910, EBI-2949715;
CC Q8IYS1; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-11339910, EBI-3957672;
CC Q8IYS1; P50221: MEOX1; NbExp=3; IntAct=EBI-11339910, EBI-2864512;
CC Q8IYS1; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-11339910, EBI-5662487;
CC Q8IYS1; Q93015-2: NAA80; NbExp=3; IntAct=EBI-11339910, EBI-12126220;
CC Q8IYS1; Q8IYS1: PM20D2; NbExp=3; IntAct=EBI-11339910, EBI-11339910;
CC Q8IYS1; P78424: POU6F2; NbExp=3; IntAct=EBI-11339910, EBI-12029004;
CC Q8IYS1; P25786: PSMA1; NbExp=3; IntAct=EBI-11339910, EBI-359352;
CC Q8IYS1; Q04864-2: REL; NbExp=3; IntAct=EBI-11339910, EBI-10829018;
CC Q8IYS1; O14924: RGS12; NbExp=3; IntAct=EBI-11339910, EBI-7358493;
CC Q8IYS1; O75695: RP2; NbExp=3; IntAct=EBI-11339910, EBI-7996807;
CC Q8IYS1; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-11339910, EBI-6257312;
CC Q8IYS1; Q8IYX7: SAXO1; NbExp=3; IntAct=EBI-11339910, EBI-3957636;
CC Q8IYS1; O15304-2: SIVA1; NbExp=3; IntAct=EBI-11339910, EBI-12372219;
CC Q8IYS1; Q9BX59: TAPBPL; NbExp=3; IntAct=EBI-11339910, EBI-12017416;
CC Q8IYS1; P48775: TDO2; NbExp=3; IntAct=EBI-11339910, EBI-743494;
CC -!- SIMILARITY: Belongs to the peptidase M20A family. {ECO:0000305}.
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DR EMBL; AK302464; BAG63754.1; -; mRNA.
DR EMBL; AL353135; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471051; EAW48559.1; -; Genomic_DNA.
DR EMBL; BC035036; AAH35036.2; -; mRNA.
DR EMBL; BC045583; AAH45583.1; -; mRNA.
DR EMBL; BX640865; CAE45925.1; -; mRNA.
DR CCDS; CCDS34499.1; -.
DR RefSeq; NP_001010853.1; NM_001010853.2.
DR AlphaFoldDB; Q8IYS1; -.
DR SMR; Q8IYS1; -.
DR BioGRID; 126427; 67.
DR IntAct; Q8IYS1; 30.
DR STRING; 9606.ENSP00000275072; -.
DR MEROPS; M20.021; -.
DR GlyGen; Q8IYS1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IYS1; -.
DR PhosphoSitePlus; Q8IYS1; -.
DR BioMuta; PM20D2; -.
DR DMDM; 121944459; -.
DR EPD; Q8IYS1; -.
DR jPOST; Q8IYS1; -.
DR MassIVE; Q8IYS1; -.
DR MaxQB; Q8IYS1; -.
DR PaxDb; Q8IYS1; -.
DR PeptideAtlas; Q8IYS1; -.
DR PRIDE; Q8IYS1; -.
DR ProteomicsDB; 71220; -.
DR Antibodypedia; 31855; 108 antibodies from 22 providers.
DR DNASU; 135293; -.
DR Ensembl; ENST00000275072.5; ENSP00000275072.4; ENSG00000146281.6.
DR GeneID; 135293; -.
DR KEGG; hsa:135293; -.
DR MANE-Select; ENST00000275072.5; ENSP00000275072.4; NM_001010853.3; NP_001010853.1.
DR UCSC; uc003pmz.6; human.
DR CTD; 135293; -.
DR DisGeNET; 135293; -.
DR GeneCards; PM20D2; -.
DR HGNC; HGNC:21408; PM20D2.
DR HPA; ENSG00000146281; Low tissue specificity.
DR MIM; 615913; gene.
DR neXtProt; NX_Q8IYS1; -.
DR OpenTargets; ENSG00000146281; -.
DR PharmGKB; PA162399803; -.
DR VEuPathDB; HostDB:ENSG00000146281; -.
DR eggNOG; ENOG502QQPD; Eukaryota.
DR GeneTree; ENSGT00390000003365; -.
DR HOGENOM; CLU_031812_1_1_1; -.
DR InParanoid; Q8IYS1; -.
DR OMA; EHHAHGV; -.
DR OrthoDB; 455218at2759; -.
DR PhylomeDB; Q8IYS1; -.
DR TreeFam; TF332656; -.
DR PathwayCommons; Q8IYS1; -.
DR SignaLink; Q8IYS1; -.
DR BioGRID-ORCS; 135293; 8 hits in 1025 CRISPR screens.
DR ChiTaRS; PM20D2; human.
DR GenomeRNAi; 135293; -.
DR Pharos; Q8IYS1; Tdark.
DR PRO; PR:Q8IYS1; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q8IYS1; protein.
DR Bgee; ENSG00000146281; Expressed in tibialis anterior and 192 other tissues.
DR Genevisible; Q8IYS1; HS.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016805; F:dipeptidase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0006508; P:proteolysis; IDA:MGI.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IDA:MGI.
DR InterPro; IPR036264; Bact_exopeptidase_dim_dom.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR InterPro; IPR017144; Xaa-Arg_dipeptidase.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF037226; Amidohydrolase_ACY1L2_prd; 1.
DR SUPFAM; SSF55031; SSF55031; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Hydrolase; Protease; Reference proteome.
FT CHAIN 1..436
FT /note="Xaa-Arg dipeptidase"
FT /id="PRO_0000286340"
FT VARIANT 333
FT /note="K -> E (in dbSNP:rs10944433)"
FT /id="VAR_032081"
FT CONFLICT 171
FT /note="I -> V (in Ref. 4; AAH45583)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="H -> N (in Ref. 4; AAH45583)"
FT /evidence="ECO:0000305"
FT CONFLICT 434
FT /note="A -> V (in Ref. 4; AAH45583)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 436 AA; 47776 MW; BC387E3CD2B29A94 CRC64;
MRPGGERPVE GGACNGRSEL ELLKLRSAEC IDEAAERLGA LSRAIWSQPE LAYEEHHAHR
VLTHFFEREP PAASWAVQPH YQLPTAFRAE WEPPEARAPS ATPRPLHLGF LCEYDALPGI
GHACGHNLIA EVGAAAALGV RGALEGLPRP PPPVKVVVLG TPAEEDGGGK IDLIEAGAFT
NLDVVFMAHP SQENAAYLPD MAEHDVTVKY YGKASHSASY PWEGLNALDA AVLAYNNLSV
FRQQMKPTWR VHGIIKNGGV KPNIIPSYSE LIYYFRAPSM KELQVLTKKA EDCFRAAALA
SGCTVEIKGG AHDYYNVLPN KSLWKAYMEN GRKLGIEFIS EDTMLNGPSG STDFGNVSFV
VPGIHPYFHI GSNALNHTEQ YTEAAGSQEA QFYTLRTAKA LAMTALDVIF KPELLEGIRE
DFKLKLQEEQ FVNAVE
